Home About us Contact
|
Home About us Contact | ||
|
|
||
New Metabolites (new + metabolite)
Selected AbstractsVigulariol, a New Metabolite from the Sea Pen Vigularia junceaCHEMINFORM, Issue 39 2005Jui-Hsin Su Abstract For Abstract see ChemInform Abstract in Full Text. [source] A New Metabolite with a New Substitution Pattern from the Seeds of the Chinese Yew, Taxus maireiCHEMISTRY & BIODIVERSITY, Issue 1 2007Chang-Hong Huo Abstract A new taxoid metabolite with a new substitution pattern was isolated from the methanol extract of the seeds of Taxus mairei, and its structure was established as 5,,15-dihydroxy-7,,9, -diacetoxy-11(15,1)abeo- taxa-4(20),11-dien-13-one (1) on the basis of spectral analysis including 1H- and 13C-NMR, HMQC, HMBC, NOESY, and confirmed by HR-FAB mass spectrometry. [source] Two New Metabolites, Epoxydine A and B, from Phoma sp.HELVETICA CHIMICA ACTA, Issue 1 2010Song Qin Abstract The new compounds, epoxydines A and B (1 and 2, resp.), along with the known and related metabolites, 3,6, were isolated from the fungal endophyte Phoma sp. The structures of the new compounds were elucidated by detailed spectroscopic analysis, and the relative configuration of 1 was confirmed by ROESY experiments. Preliminary studies indicated that compounds 2,5 possess good antibacterial, antifungal, and algicidal properties. Similarly, compound 1 showed antifungal and algicidal, and compound 6 antibacterial and algicidal properties. [source] Recent Progress in Biomolecular EngineeringBIOTECHNOLOGY PROGRESS, Issue 1 2000Dewey D. Y. Ryu During the next decade or so, there will be significant and impressive advances in biomolecular engineering, especially in our understanding of the biological roles of various biomolecules inside the cell. The advances in high throughput screening technology for discovery of target molecules and the accumulation of functional genomics and proteomics data at accelerating rates will enable us to design and discover novel biomolecules and proteins on a rational basis in diverse areas of pharmaceutical, agricultural, industrial, and environmental applications. As an applied molecular evolution technology, DNA shuffling will play a key role in biomolecular engineering. In contrast to the point mutation techniques, DNA shuffling exchanges large functional domains of sequences to search for the best candidate molecule, thus mimicking and accelerating the process of sexual recombination in the evolution of life. The phage-display system of combinatorial peptide libraries will be extensively exploited to design and create many novel proteins, as a result of the relative ease of screening and identifying desirable proteins. Even though this system has so far been employed mainly in screening the combinatorial antibody libraries, its application will be extended further into the science of protein-receptor or protein-ligand interactions. The bioinformatics for genome and proteome analyses will contribute substantially toward ever more accelerated advances in the pharmaceutical industry. Biomolecular engineering will no doubt become one of the most important scientific disciplines, because it will enable systematic and comprehensive analyses of gene expression patterns in both normal and diseased cells, as well as the discovery of many new high-value molecules. When the functional genomics database, EST and SAGE techniques, microarray technique, and proteome analysis by 2-dimensional gel electrophoresis or capillary electrophoresis in combination with mass spectrometer are all put to good use, biomolecular engineering research will yield new drug discoveries, improved therapies, and significantly improved or new bioprocess technology. With the advances in biomolecular engineering, the rate of finding new high-value peptides or proteins, including antibodies, vaccines, enzymes, and therapeutic peptides, will continue to accelerate. The targets for the rational design of biomolecules will be broad, diverse, and complex, but many application goals can be achieved through the expansion of knowledge based on biomolecules and their roles and functions in cells and tissues. Some engineered biomolecules, including humanized Mab's, have already entered the clinical trials for therapeutic uses. Early results of the trials and their efficacy are positive and encouraging. Among them, Herceptin, a humanized Mab for breast cancer treatment, became the first drug designed by a biomolecular engineering approach and was approved by the FDA. Soon, new therapeutic drugs and high-value biomolecules will be designed and produced by biomolecular engineering for the treatment or prevention of not-so-easily cured diseases such as cancers, genetic diseases, age-related diseases, and other metabolic diseases. Many more industrial enzymes, which will be engineered to confer desirable properties for the process improvement and manufacturing of high-value biomolecular products at a lower production cost, are also anticipated. New metabolites, including novel antibiotics that are active against resistant strains, will also be produced soon by recombinant organisms having de novo engineered biosynthetic pathway enzyme systems. The biomolecular engineering era is here, and many of benefits will be derived from this field of scientific research for years to come if we are willing to put it to good use. [source] Mass spectrometric identification and characterization of a new long-term metabolite of metandienone in human urineRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 15 2006Wilhelm Schänzer Anabolic-androgenic steroids are some of the most frequently detected drugs in amateur and professional sports. Doping control laboratories have developed numerous assays enabling the determination of administered drugs and/or their metabolic products that allow retrospectives with respect to pharmacokinetics and excretion profiles of steroids and their metabolites. A new metabolite generated from metandienone has been identified as 18-nor-17, -hydroxymethyl,17, -methyl-androst-1,4,13-trien-3-one in excretion study urine samples providing a valuable tool for the long-term detection of metandienone abuse by athletes in sports drug testing. The metabolite was characterized using gas chromatography/(tandem) mass spectrometry, liquid chromatography/tandem mass spectrometry and liquid chromatography/high-resolution/high-accuracy (tandem) mass spectrometry by characteristic fragmentation patterns representing the intact 3-keto-1,4-diene structure in combination with typical product ions substantiating the proposed C/D-ring structure of the steroid metabolite. In addition, structure confirmation was obtained by the analysis of excretion study urine specimens obtained after administration of 17-CD3 -labeled metandienone providing the deuterated analogue to the newly identified metabolite. 18-Nor-17, -hydroxymethyl,17, -methyl-androst-1,4,13-trien-3-one was determined in metandienone administration study urine specimens up to 19 days after application of a single dose of 5,mg, hence providing an extended detection period compared with commonly employed strategies. Copyright © 2006 John Wiley & Sons, Ltd. [source] A new metabolite of nodakenetin by rat liver microsomes and its quantification by RP-HPLC methodBIOMEDICAL CHROMATOGRAPHY, Issue 2 2010Peng Zhang Abstract The biotransformation of nodakenetin (NANI) by rat liver microsomes in vitro was investigated. Two major polar metabolites were produced by liver microsomes from phenobarbital-pretreated rats and detected by reversed-phase high-performance liquid chromatography (RP-HPLC) analysis. The chemical structures of two metabolites were firmly identified as 3,(R)-hydroxy-nodakenetin-3,-ol and 3,(S)-hydroxy-nodakenetin-3,-ol, respectively, on the basis of their 1H-NMR, MS and optical rotation analysis. The latter was a new compound. A sensitive, selective and simple RP-HPLC method has been developed for the simultaneous determination of NANI and its two major metabolites in rat liver microsomes. Chromatographic conditions comprise a C18 column, a mobile phase with MeOH-H2O (40 : 60, v/v), a total run time of 40 min, and ultraviolet absorbance detection at 330 nm. In the rat heat-inactivated liver microsomal supernatant, the lower limits of detection and quantification of metabolite I, metabolite II and NANI were 5.0, 2.0, 10.0 ng/mL and 20.0, 5.0, 50.0 ng/mL, respectively, and their calibration curves were linear over the concentration range 50,400, 20,120 and 150,24000 ng/mL, respectively. The results provided a firm basis for further evaluating the pharmacokinetics and clinical efficacy of NANI. Copyright © 2009 John Wiley & Sons, Ltd. [source] Trichocladinols A,C, Cytotoxic Metabolites from a Cordyceps -Colonizing Ascomycete Trichocladium opacumEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 32 2009Huijuan Guo Abstract Trichocladinols A,C (1,3), three new metabolites, and the known massarigenin A (4), have been isolated from cultures of a Cordyceps -colonizing ascomycete Trichocladium opacum. Their structures were elucidated by NMR spectroscopy and X-ray crystallography. The absolute configuration of 1 was assigned by using the modified Mosher method and that of 3 was determined by X-ray crystallographic analysis of its (S)-MTPA ester. Compounds 1,3 showed modest cytotoxic effects against the human tumor cell lines HeLa and MCF-7. Structurally, compounds 1 and 2 possess a previously undescribed 2,9-dioxatricyclo[5.2.1.03,8]dec-4-ene skeleton.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Secondary Metabolites of Phomopsis sp.EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 18 2009XZ-2, an Endophytic Fungus from Camptothecaacuminate Abstract Eleven new metabolites, including nine lovastatin analogues [oblongolides N,V (1,2 and 5,11), which were defined as naphthalene-type fungal polyketides], one linear furanopolyketide (13) and a monoterpene named dihydroxysabinane (14), together with four known compounds including oblongolides B (3) and C (4), one linear furanopolyketide (12) and the sesterterpene terpestacin (15), were isolated from the endophytic fungal strain Phomopsis sp. XZ-26 of Camptotheca acuminate. Their structures were elucidated by spectroscopic analyses including HR-ESI-MS, 1H and 13C NMR, 2D NMR (HMQC, HMBC, 1H- 1H COSY and NOESY), and X-ray single-crystal analysis. The antimicrobial activities of 1,5, 8, 10 and 13,15 were evaluated, but none showed a substantial effect. Additionally, a hypothetical biosynthetic pathway for oblongolides was proposed.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Primary and secondary metabolism, and post-translational protein modifications, as portrayed by proteomic analysis of Streptomyces coelicolorMOLECULAR MICROBIOLOGY, Issue 4 2002A. R. Hesketh Summary The newly sequenced genome of Streptomyces coelicolor is estimated to encode 7825 theoretical proteins. We have mapped approximately 10% of the theoretical proteome experimentally using two-dimensional gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry. Products from 770 different genes were identified, and the types of proteins represented are discussed in terms of their anno-tated functional classes. An average of 1.2 proteins per gene was observed, indicating extensive post-translational regulation. Examples of modification by N-acetylation, adenylylation and proteolytic processing were characterized using mass spectrometry. Proteins from both primary and certain secondary metabolic pathways are strongly represented on the map, and a number of these enzymes were identified at more than one two-dimensional gel location. Post-translational modification mechanisms may therefore play a significant role in the regulation of these pathways. Unexpectedly, one of the enzymes for synthesis of the actinorhodin polyketide antibiotic appears to be located outside the cytoplasmic compartment, within the cell wall matrix. Of 20 gene clusters encoding enzymes characteristic of secondary metabolism, eight are represented on the proteome map, including three that specify the production of novel metabolites. This information will be valuable in the characterization of the new metabolites. [source] Characterization of Ganstigmine metabolites in hepatocytes by low- and high-resolution mass spectrometry coupled with liquid chromatographyRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 15 2003Nicola Pelizzi In order to deepen the understanding of the metabolism of Ganstigmine, a new acetylcholinesterase inhibitor under evaluation for the treatment of Alzheimer's disease, samples obtained by incubating the drug with female rat hepatocytes were investigated by low-resolution liquid chromatography/tandem mass spectrometry (LC/MS/MS). The results confirmed the formation of most of the phase I metabolites already demonstrated, but also three new species. The combination of high-resolution quadrupole time-of-flight (Q-TOF) LC/MS and LC/MS/MS measurements, and the evaluation of the more reasonable metabolic routes, allowed the identification of the new metabolites as Geneseroline-glucuronide and oxidized and rearranged Ganstigmine. Analogous investigations were made using hepatocytes from male rat and dog, and both gender monkeys and humans, to compare the metabolic patterns. The results did not indicate substantial differences in terms of numbers and abundances of detected metabolites among the considered species, and also between male and female hepatocytes within each species. Copyright © 2003 John Wiley & Sons, Ltd. [source] Ecology-based screen identifies new metabolites from a Cordyceps -colonizing fungus as cancer cell proliferation inhibitors and apoptosis inducersCELL PROLIFERATION, Issue 6 2009Y. Chen Objectives:, This study aims to identify new anti-cancer agents from Cordyceps -colonizing fungi, using an ecology-based approach. It also aims to explore their anti-cell proliferative mechanisms, and to evaluate their anti-tumour effects in vivo. Materials and methods:, Extracts from Cordyceps -colonizing fungi were tested on HeLa cells, and active extracts were separated to obtain anti-tumour metabolites; their structures were elucidated by mass and nuclear magnetic resonance spectroscopy. Cell cycle analysis was evaluated using flow cytometry. Tumour formation assays were performed using C57BL/6J mice. Results:, Based on ecological considerations, the selected extracts were subjected to initial anti-tumour screening. Bioassay-guided fractionation of the active extract afforded two new epipolythiodioxopiperazines, named gliocladicillins A (1) and B (2). (A) 1 and B (2) inhibited growth of HeLa, HepG2 and MCF-7 tumour cells. Further study demonstrated that both preparations arrested the cell cycle at G2/M phase in a dose-dependent manner, and induced apoptosis through up-regulation of expression of p53, p21, and cyclin B, and activation of caspases-8, -9 and -3. These data imply that gliocladicillins A (1) and B (2) induce tumour cell apoptosis through both extrinsic and intrinsic pathways. In addition, in vivo studies showed that they displayed significant inhibitory effects on cell population growth of melanoma B16 cells imlanted into immunodeficient mice. Conclusions:, Gliocladicillins A (1) and B (2) are effective anti-tumour agents in vitro and in vivo and should be further evaluated for their potential in clinical use. [source] Generation of New Landomycins with Altered Saccharide Patterns through Over-expression of the Glycosyltransferase Gene lanGT3 in the Biosynthetic Gene Cluster of Landomycin A in Streptomyces cyanogenus S-136CHEMBIOCHEM, Issue 1 2007Lili Zhu Dr. Abstract Two novel landomycin compounds, landomycins I and J, were generated with a new mutant strain of Streptomyces cyanogenus in which the glycosyltransferase that is encoded by lanGT3 was over-expressed. This mutant also produced the known landomycins A, B, and D. All these compounds consist of the same polyketide-derived aglycon but differ in their sugar moieties, which are chains of different lengths. The major new metabolite, landomycin J, was found to consist of landomycinone with a tetrasaccharide chain attached. Combined with previous results of the production of landomycin E (which contains three sugars) by the LanGT3, mutant strain (obtained by targeted gene deletion of lanGT3), it was verified that LanGT3 is a D -olivosyltransferase responsible for the transfer of the fourth sugar required for landomycin A biosynthesis. The experiments also showed that gene over-expression is a powerful method for unbalancing biosynthetic pathways in order to generate new metabolites. The cytotoxicity of the new landomycins,compared to known ones,was assessed by using three different tumor cell lines, and their structure,activity relationship (SAR) with respect to the length of the deoxysugar side chain was deduced from the results. [source] Joziknipholones A and B: The First Dimeric Phenylanthraquinones, from the Roots of Bulbine frutescensCHEMISTRY - A EUROPEAN JOURNAL, Issue 5 2008Gerhard Bringmann Prof. Abstract From the roots of the African plant Bulbine frutescens (Asphodelaceae), two unprecedented novel dimeric phenylanthraquinones, named joziknipholones A and B, possessing axial and centrochirality, were isolated, together with six known compounds. Structural elucidation of the new metabolites was achieved by spectroscopic and chiroptical methods, by reductive cleavage of the central bond between the monomeric phenylanthraquinone and -anthrone portions with sodium dithionite, and by quantum chemical CD calculations. Based on the recently revised absolute axial configuration of the parent phenylanthraquinones, knipholone and knipholone anthrone, the new dimers were attributed to possess the P -configuration (i.e., with the acetyl portions below the anthraquinone plane) at both axes in the case of joziknipholone A, whereas in joziknipholone B, the knipholone part was found to be M -configured. Joziknipholones A and B are active against the chloroquine resistant strain K1 of the malaria pathogen, Plasmodium falciparum, and show moderate activity against murine leukemic lymphoma L5178y cells. [source] Glycoalkaloids as Biomarkers for Recognition of Cultivated, Wild, and Somatic Hybrids of PotatoCHEMISTRY & BIODIVERSITY, Issue 4 2009Salvatore Savarese Abstract Cultivated and wild potato species synthesize a wide variety of steroidal glycoalkaloids (GAs). During breeding programs, species genomes are often put together through either sexual or somatic hybridization. Therefore, the determination of the GA composition of hybrids is very important in that it may affect either human consumption, or resistance to pathogen and pests. Here, we report the results of GA analysis performed on wild Solanum bulbocastanum, haploids of cultivated potato S. tuberosum and their interspecific somatic hybrids. GAs were extracted from tubers and analyzed by HPLC. HPLC Profile of S. tuberosum haploids showed, as expected, the presence of , -solanine and , -chaconine. The profile of S. bulbocastanum extract showed lack of , -solanine and , -chaconine, and the presence of four GAs. The GA pattern of the somatic hybrids was the sum of their parents' profile. This represents a noteworthy tool for their unequivocal recognition. Interestingly, two hybrids produced not only GAs of both parents but also new compounds to be further investigated. This provided evidence that somatic hybridization induced the synthesis of new metabolites. The nature of the probable unidentified GAs associated to S. bulbocastanum and its somatic hybrids was ascertained by chemical degradation and spectroscopic analysis of their aglycones and sugar moieties. Our results suggest their close relation with GAs of both wild and cultivated potato species. [source] Microbial Transformations of Gelomulide G: A Member of the Rare Class of Diterpene LactonesCHEMISTRY & BIODIVERSITY, Issue 10 2005Iqbal Choudhary Microbial transformation of gelomulide G (3,,6,- diacetoxy-8,,14,- epoxyabiet-13(15)-en-16,12-olide, 1) was carried out. Incubation of 1 with Aspergillus niger afforded two new metabolites, 3,,6,- diacetoxy-8,,14,- dihydroxyabiet-13(15)-en-16,12-olide (2) and 3,,6,- diacetoxy-14,- hydroxyabieta-8(9),13(15)-dien-16,12-olide (3). While Cunninghamella elegans afforded the 14-epimer of 2, i.e., 3,,6,- diacetoxy-8,,14,- dihydroxyabiet-13(15)-en-16,12-olide (4), along with 3, -acetoxy-6,- hydroxy-8,,14,- epoxyabiet-13(15)-en-16,12-olide (5). The structures of the transformed products 2,5 were deduced to be new on the basis of MS and NMR data. [source] | |||||||||||||||||||||||||